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1.  A Comprehensive Availability Modeling and Analysis of a Virtualized Servers System Using Stochastic Reward Nets 
The Scientific World Journal  2014;2014:165316.
It is important to assess availability of virtualized systems in IT business infrastructures. Previous work on availability modeling and analysis of the virtualized systems used a simplified configuration and assumption in which only one virtual machine (VM) runs on a virtual machine monitor (VMM) hosted on a physical server. In this paper, we show a comprehensive availability model using stochastic reward nets (SRN). The model takes into account (i) the detailed failures and recovery behaviors of multiple VMs, (ii) various other failure modes and corresponding recovery behaviors (e.g., hardware faults, failure and recovery due to Mandelbugs and aging-related bugs), and (iii) dependency between different subcomponents (e.g., between physical host failure and VMM, etc.) in a virtualized servers system. We also show numerical analysis on steady state availability, downtime in hours per year, transaction loss, and sensitivity analysis. This model provides a new finding on how to increase system availability by combining both software rejuvenations at VM and VMM in a wise manner.
PMCID: PMC4138929  PMID: 25165732
2.  Structures of a γ-aminobutyrate (GABA) transaminase from the s-triazine-degrading organism Arthrobacter aurescens TC1 in complex with PLP and with its external aldimine PLP–GABA adduct 
The structure of the γ-aminobutyrate transaminase A1R958 from A. aurescens TC1 in complex with PLP–GABA reveals the active-site determinants of GABA binding in this enzyme.
Two complex structures of the γ-aminobutyrate (GABA) transaminase A1R958 from Arthrobacter aurescens TC1 are presented. The first, determined to a resolution of 2.80 Å, features the internal aldimine formed by reaction between the ∊-amino group of Lys295 and the cofactor pyridoxal phosphate (PLP); the second, determined to a resolution of 2.75 Å, features the external aldimine adduct formed between PLP and GABA in the first half-reaction. This is the first structure of a microbial GABA transaminase in complex with its natural external aldimine and reveals the molecular determinants of GABA binding in this enzyme.
PMCID: PMC3497974  PMID: 23027742
γ-aminobutyrate transaminase; A1R958; Arthrobacter aurescens TC1
3.  The experiences of implementing generic medicine policy in eight countries: A review and recommendations for a successful promotion of generic medicine use 
Generic medicines are clinically interchangeable with original brand medicines and have the same quality, efficacy and safety profiles. They are, nevertheless, much cheaper in price. Thus, while providing the same therapeutic outcomes, generic medicines lead to substantial savings for healthcare systems. Therefore, the quality use of generic medicines is promoted in many countries. In this paper, we reviewed the role of generic medicines in healthcare systems and the experiences of promoting the use of generic medicines in eight selected countries, namely the United States (US), the United Kingdom (UK), Sweden, Finland, Australia, Japan, Malaysia and Thailand. The review showed that there are different main policies adopted to promote generic medicines such as generic substitution in the US, generic prescribing in the UK and mandatory generic substitution in Sweden and Finland. To effectively and successfully implement the main policy, different complementary policies and initiatives were necessarily introduced. Barriers to generic medicine use varied between countries from negative perceptions about generic medicines to lack of a coherent generic medicine policy, while facilitators included availability of information about generic medicines to both healthcare professionals and patients, brand interchangeability guidelines, regulations that support generic substitution by pharmacists, and incentives to both healthcare professionals and patients.
PMCID: PMC4281627  PMID: 25561861
Generic medicines; Health system; Generic policy; Generic substitution; Pharmacists; Physicians
4.  Prevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program – Vietnam 
PLoS ONE  2013;8(4):e62213.
An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm3 for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam.
Serum samples were collected and stored during 2009–2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm3 were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines.
Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm3 were available for CrAg testing. Median CD4 count was 40 (range 0–99) cells/mm3. Nine (4%; 95% CI 2–7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3–11%) than in North Vietnam (2%; 95% CI 0–6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively.
CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.
PMCID: PMC3633872  PMID: 23626792
5.  Genome Sequence of an Unusual Human G10P[8] Rotavirus Detected in Vietnam 
Journal of Virology  2012;86(18):10236-10237.
A rare human G10P[8] rotavirus with a reassortment between bovine and human viruses was detected from a patient with acute gastroenteritis in Vietnam. Genetic analysis using complete coding sequences of all segments showed a genomic constellation of this virus of G10-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Its VP7 region was genetically related to that of a bovine rotavirus derived from Australia (strain VICG10.01), whereas all other genes were identical to those of a human rotavirus derived from Australia (strain Victoria/CK00047). These results indicate a possibility that the reassortment of the rotavirus was caused by immune escape in Australia and the rotavirus was carried to Vietnam. Additionally, this finding will help further understanding the evolution of rotaviruses circulating in Vietnam.
PMCID: PMC3446621  PMID: 22923797
6.  Implementation of Web-Based Respondent-Driven Sampling among Men Who Have Sex with Men in Vietnam 
PLoS ONE  2012;7(11):e49417.
Lack of representative data about hidden groups, like men who have sex with men (MSM), hinders an evidence-based response to the HIV epidemics. Respondent-driven sampling (RDS) was developed to overcome sampling challenges in studies of populations like MSM for which sampling frames are absent. Internet-based RDS (webRDS) can potentially circumvent limitations of the original RDS method. We aimed to implement and evaluate webRDS among a hidden population.
Methods and Design
This cross-sectional study took place 18 February to 12 April, 2011 among MSM in Vietnam. Inclusion criteria were men, aged 18 and above, who had ever had sex with another man and were living in Vietnam. Participants were invited by an MSM friend, logged in, and answered a survey. Participants could recruit up to four MSM friends. We evaluated the system by its success in generating sustained recruitment and the degree to which the sample compositions stabilized with increasing sample size.
Twenty starting participants generated 676 participants over 24 recruitment waves. Analyses did not show evidence of bias due to ineligible participation. Estimated mean age was 22 years and 82% came from the two large metropolitan areas. 32 out of 63 provinces were represented. The median number of sexual partners during the last six months was two. The sample composition stabilized well for 16 out of 17 variables.
Results indicate that webRDS could be implemented at a low cost among Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of Internet-using MSM and other hidden groups.
PMCID: PMC3495883  PMID: 23152902
7.  Biochemical studies of the Saccharomyces cerevisiae Mph1 helicase on junction-containing DNA structures 
Nucleic Acids Research  2011;40(5):2089-2106.
Saccharomyces cerevisiae Mph1 is a 3–5′ DNA helicase, required for the maintenance of genome integrity. In order to understand the ATPase/helicase role of Mph1 in genome stability, we characterized its helicase activity with a variety of DNA substrates, focusing on its action on junction structures containing three or four DNA strands. Consistent with its 3′ to 5′ directionality, Mph1 displaced 3′-flap substrates in double-fixed or equilibrating flap substrates. Surprisingly, Mph1 displaced the 5′-flap strand more efficiently than the 3′ flap strand from double-flap substrates, which is not expected for a 3–5′ DNA helicase. For this to occur, Mph1 required a threshold size (>5 nt) of 5′ single-stranded DNA flap. Based on the unique substrate requirements of Mph1 defined in this study, we propose that the helicase/ATPase activity of Mph1 play roles in converting multiple-stranded DNA structures into structures cleavable by processing enzymes such as Fen1. We also found that the helicase activity of Mph1 was used to cause structural alterations required for restoration of replication forks stalled due to damaged template. The helicase properties of Mph1 reported here could explain how it resolves D-loop structure, and are in keeping with a model proposed for the error-free damage avoidance pathway.
PMCID: PMC3300029  PMID: 22090425
8.  Genetic and functional interactions between Mus81–Mms4 and Rad27 
Nucleic Acids Research  2010;38(21):7611-7625.
The two endonucleases, Rad27 (yeast Fen1) and Dna2, jointly participate in the processing of Okazaki fragments in yeasts. Mus81–Mms4 is a structure-specific endonuclease that can resolve stalled replication forks as well as toxic recombination intermediates. In this study, we show that Mus81–Mms4 can suppress dna2 mutational defects by virtue of its functional and physical interaction with Rad27. Mus81–Mms4 stimulated Rad27 activity significantly, accounting for its ability to restore the growth defects caused by the dna2 mutation. Interestingly, Rad27 stimulated the rate of Mus81–Mms4 catalyzed cleavage of various substrates, including regressed replication fork substrates. The ability of Rad27 to stimulate Mus81–Mms4 did not depend on the catalytic activity of Rad27, but required the C-terminal 64 amino acid fragment of Rad27. This indicates that the stimulation was mediated by a specific protein–protein interaction between the two proteins. Our in vitro data indicate that Mus81–Mms4 and Rad27 act together during DNA replication and resolve various structures that can impede normal DNA replication. This conclusion was further strengthened by the fact that rad27 mus81 or rad27 mms4 double mutants were synergistically lethal. We discuss the significance of the interactions between Rad27, Dna2 and Mus81–Mms4 in context of DNA replication.
PMCID: PMC2995070  PMID: 20660481
9.  Prevalence and Risk Factors Associated with HIV Infection Among Men Having Sex with Men in Ho Chi Minh City, Vietnam 
AIDS and Behavior  2007;12(3):476-482.
To learn more about risk behaviors among men who have sex with men (MSM) in Vietnam and their prevalence of HIV, we conducted a study among MSM in Ho Chi Minh City (HCMC) to determine HIV-1 prevalence and behaviors associated with infection. This consisted of formative (35 MSM) and cross-sectional (600 MSM) studies at 72 sites, including 75 transvestites, 55 bisexuals, 10 sex workers, and 460 other MSM. Only 5.3% cohabited with a wife/girlfriend, but 30% reported ever having sex with a female. Prevalence of HIV was 8%, ranging from 33% in sex workers to 7% among transvestites and other MSM. Injecting drugs, selling sex, being 20–40 years old, having less than 6 years of education, and having more than five male anal sex partners in the past month were associated with being HIV-infected. MSM are an HIV bridge group, and should be included in sentinel surveillance. Targeted interventions should be implemented.
PMCID: PMC2903539  PMID: 17594139
HIV; Men having sex with men (MSM); Vietnam; Injection drug users (IDUs); Commercial sex workers (CSWs)
10.  Involvement of Vts1, a structure-specific RNA-binding protein, in Okazaki fragment processing in yeast 
Nucleic Acids Research  2009;38(5):1583-1595.
The non-essential VTS1 gene of Saccharomyces cerevisiae is highly conserved in eukaryotes and encodes a sequence- and structure-specific RNA-binding protein. The Vts1 protein has been implicated in post-transcriptional regulation of a specific set of mRNAs that contains its-binding site at their 3′-untranslated region. In this study, we identified VTS1 as a multi-copy suppressor of dna2-K1080E, a lethal mutant allele of DNA2 that lacks DNA helicase activity. The suppression was allele-specific, since overexpression of Vts1 did not suppress the temperature-dependent growth defects of dna2Δ405N devoid of the N-terminal 405-amino-acid residues. Purified recombinant Vts1 stimulated the endonuclease activity of wild-type Dna2, but not the endonuclease activity of Dna2Δ405N, indicating that the activation requires the N-terminal domain of Dna2. Stimulation of Dna2 endonuclease activity by Vts1 appeared to be the direct cause of suppression, since the multi-copy expression of Dna2-K1080E suppressed the lethality observed with its single-copy expression. We found that vts1Δ dna2Δ405N and vts1Δdna2-7 double mutant cells displayed synergistic growth defects, in support of a functional interaction between two genes. Our results provide both in vivo and in vitro evidence that Vts1 is involved in lagging strand synthesis by modulating the Dna2 endonuclease activity that plays an essential role in Okazaki fragment processing.
PMCID: PMC2836565  PMID: 20007605
11.  Soft Tissue Coverage at the Resource-challenged Facility 
Covering soft tissue defects remains challenging for orthopaedic surgeons, especially those in resource-challenged facilities. Covering tissue defects follow a plan from simple to complex: primary closure, local flap, area flap, pedicle flap, and free flap. I will limit my discussion to the role of latter two. At the district-level hospital in Vietnam, pedicle flaps are generally more useful, so I will discuss free flaps only briefly. The choices of pedicle flaps include: kite flap, posterior interosseous flap, radial flap (Chinese flap), neurocutaneous flap, anterolateral thigh fasciocutaneous flap, gastrocnemius flap, sural flap, posterior leg flaps; we typically use a free flap with the latissimus dorsi. Soft tissue coverage with pedicle flaps has many advantages: reliability, relatively easy harvest, and good blood supply. Free flaps with microanastomosis have an important place in covering difficult medium- or large-sized soft tissue defects but also require more instruments and more highly trained surgeons.
PMCID: PMC2584312  PMID: 18665433
12.  Prevalence of Bordetella pertussis and Bordetella parapertussis in Samples Submitted for RSV Screening 
The clinical presentation of Bordetella pertussis can overlap with that of respiratory syncytial virus (RSV); however, management differs.
First, the prevalence of B. pertussis is less than 2% among patients screened for RSV, and second the prevalence of B. parapertussis is also less than 2% among these patients.
Nasal washings submitted to a clinical laboratory for RSV screening were tested for B. pertussis and B. parapertussis, using species-specific real-time polymerase chain reaction (PCR) assays. These were optimized to target conserved regions within a complement gene and the CarB gene, respectively. A Bordetella spp. genus-specific real-time PCR assay was designed to detect the Bhur gene of B. pertussis, B. parapertussis, and B. bronchiseptica. RSV A and B subtypes were tested by reverse transcription-PCR.
Four hundred and eighty-nine clinical samples were tested. There was insufficient material to complete testing for one B. pertussis, 10 RSV subtype A, and four RSV subtype B assays. Bordetella pertussis was detected in 3/488 (0.6%) (95% CI 0.1% to 1.8%), while B. parapertussis was detected in 5/489 (1.0%) (95% CI 0.3% to 2.4%). Dual infection of B. pertussis with RSV and of B. parapertussis with RSV occurred in two and in three cases respectively. RSV was detected by PCR in 127 (26.5%).
The prevalence of B. pertussis in nasal washings submitted for RSV screening was less than 2%. The prevalence of parapertussis may be higher than 2%. RSV with B. pertussis and RSV with B. parapertussis coinfection do occur.
PMCID: PMC2672259  PMID: 19561728
13.  Isolation and Molecular Characterization of Aichi Viruses from Fecal Specimens Collected in Japan, Bangladesh, Thailand, and Vietnam▿  
Journal of Clinical Microbiology  2007;45(7):2287-2288.
Aichi virus is a new member of the family Picornaviridae, genus Kobuvirus, and is associated with human gastroenteritis. This study detected Aichi virus in 28 of 912 fecal specimens which were negative for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus and were collected in Japan, Bangladesh, Thailand, and Vietnam during 2002 to 2005.
PMCID: PMC1932998  PMID: 17522267

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